Formaldehyde → HCID 53312153, compound

HRID 924334Notes

Reaction equation

HRID 924334 reaction equation
[C:1]([C@@H:9]1[CH2:13][CH:12]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:17][CH:16]=2)[N:11](/C=C/C2C=CC=CC=2)C1=O)(=O)C1C=CC=CC=1.C=O.CCCC[N+:42]([CH2:51]CCC)([CH2:47][CH2:48][CH2:49][CH3:50])CCCC.[OH-].[C:56]([O-:59])([O-])=O.[K+].[K+]>O1CCCC1.[Cl-].[Na+].O>[C:18]1([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:17]=[CH:16][C:15]([CH2:14][C@H:12]2[N:11]([CH2:51][N:42]3[CH2:47][CH2:48][CH2:49][CH2:50]3)[C:56](=[O:59])[C:9](=[CH2:1])[CH2:13]2)=[CH:20][CH:19]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 11430Potassium CarbonateHCID 2723671Tetrabutylammonium HydroxideHCID 86673650HCID 86673650, compound

Product 1

HCID 53312153HCID 53312153, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
50 °C

Procedure

The mixture of (R/S)-3-Benzoyl-(S)-5-biphenyl-4-ylmethyl-1-pyrrolidin-1-ylmethyl-pyrrolidin-2-one (4a, R1=pyrrolidinylmethyl, R4=phenyl) (0.44 g, 1 mmol), formaldehyde (37% in water, 0.24 g, 3 mmol), TBAH (6.5 mg, 0.01 mmol) and K2CO3 (0.28 g, 1.3 mmol, dissolved in 1 mL water) in 5 mL dry tetrahydrofuran was heated to 50° C. and stirred for 2 hours. Then the reaction mixture is diluted with 5 mL brine and stirred for 15 min, stop stirring, and remove the lower aqueous layer. the organic phase is then concentrated in vacuo. ethyl acetate 10 mL is added, filtered and the filtrate concentrated and purified by column chromatography eluting with 5:1 heptane/ethyl acetate to afford (R)-5-Biphenyl-4-ylmethyl-3-methylene-1-pyrrolidin-1-ylmethyl-pyrrolidin-2-one (1a, R1=pyrrolidinylmethyl). 1HNMR (400 MHz, CDCl3): 1.68 (m, 4H, 2×CH2CH2), 2.06 (m, 1H, 3-CHH), 2.31 (m, 1H, 3-CHH), 2.51 (m, 4H, 2×NCH2), 2.67 (d, 1H, 5-CHH), 2.65 (dd, 1H, N—CHH), 3.15 (dd, 1H, N—CHH), 2.92 (d, 1H, 5-CHH), 4.01 (m, 1H, 4-CH), 5.54 (d, 1H, ═CHH), 6.02 (d, 1H, ═CHH), 7.20-7.80 (14H, m, aromatic).

Workup

  1. stirringstirred for 15 min
  2. stirringstop stirring
  3. customremove the lower aqueous layer
  4. concentrationthe organic phase is then concentrated in vacuo
  5. additionethyl acetate 10 mL is added
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated
  8. custompurified by column chromatography
  9. washeluting with 5:1 heptane/ethyl acetate

Sources & evidence

ORD record
ord-2ff89f15d3ab43cf8924489b4f991de4
Source dataset
uspto-grants-2016_03
Patent number
US09278908B2

Reaction notes

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